DETECT-AD: Digital Evaluations and Technologies Enabling Clinical Translation for Alzheimer's Disease

DETECT-AD：数字评估和技术支持阿尔茨海默病的临床转化

• 批准号: 10483176
• 负责人: JEFFREY A KAYE
• 金额: $ 206.81万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483176
• 关键词: Adverse event; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer' s disease therapy; Amyloid; Amyloid beta-Protein; Biological Markers; Blood Vessels; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Cognition; Cognitive; Computers; Data; Development; Devices; Disease; Early Diagnosis; Elderly; Enrollment; Environment; Evaluation; Failure; Foundations; Gait speed; Goals; Health; Home; Homocysteine; Hospitals; Image; Impaired cognition; Individual; Inflammation; Injury; Interleukins; Life; Life Experience; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measures; Mediating; Memory; Methodology; Methods; Monitor; Moods; Multivitamin; Nerve Degeneration; Nutritional; Oregon; Pain; Participant; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Physiological; Placebos; Positron-Emission Tomography; Protocols documentation; Questionnaires; Reporting; Research; Research Design; Risk; Sample Size; Sleep; Socialization; System; Technology; Testing; Time; Translating; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factors; Visit; advanced disease; base; blood-based biomarker; clinical translation; cognitive function; cognitive testing; digital; effective therapy; efficacy testing; fall injury; functional decline; improved; intercellular cell adhesion molecule; pre-clinical; primary outcome; prospective; remote assessment; response; sensor; simulation; social engagement; therapy development; treatment response; β-amyloid burden

Project Summary This study (DETECT-AD or Digital Evaluations and Technologies Enabling Clinical Translation for AD) objective is to fundamentally asymptomatic improve assessment of meaningful cognitive function in early pre- or Alzheimer's Disease (AD) using largely passive home-based digital assessment methods.To achieve this goal the approach will be tested in a prospective 36-month pre-clinical AD trial simulation using a current, sharable, technology agnostic, home-based assessment platform, continuously generating passive and interactive sensor-derived digital biomarkers (DBs) and metrics of everyday cognition and function (digital indicators of active life status or DIALS). The platform also allows for remote capture of conventional clinical assessments. Participants with defined amyloid status (Aβ-high vs. Aβ-low based on relative amyloid PET burdens) will be enrolled. Aβ-high participants will progress as if they were receiving placebo; those with lower Aβ burdens will have less progression, simulating effective treatment. Participants will be asked to take a daily multivitamin as a study `drug' to mimic trial conditions. The primary outcome will be change in the DBs and composite DIALS from four key domains: mobility (gait speeds), cognition (computer usage), sleep (sleep times), socialization (time out of home). Specific Aims are to: 1) Determine rates of progression of DBs (of mobility, cognition, sleep and social engagement) individually and as an aggregate metric (the DIALS) in FDA stage 1-3 AD (Aβ-high vs. Aβ-low) participants, by establishing early base rates (first months of monitoring) of progression, and then, longitudinal change; 2) Establish the utility of these DBs compared to conventional measures (CDR-SoB, ADCS-PACC) used in trials; and 3) Investigate Exploratory Aims examining several high-value features of these DBs for application in trials and related studies including: 3.1) Correlate DBs and DIALS with conventional imaging and blood-based biomarkers of inflammation, neurodegeneration, vascular risk or injury, and nutritional health; 3.2) Determine the change over time of embedded “cognitive clocks” (time to complete regular weekly online report queries and monthly cognitive tests); 3.3) Establish adverse event fluctuations over time (mood; illness; pain; ER, doctor, hospital visits; injury; non-study medication changes) via weekly remote assessment; and 3.4) Assess the study partner's DBs change relative to the person with AD (mobility, sleep, social engagement). study thus Successful completion of this will provide foundational validated DB and DIALS data improving treatment response readout sensitivity; advancing AD clinical trial capability and capacity.The intent is to not only validate a single app or device, but to advance ecologically valid multi-domain assessment, as well as an entire trials-environment specific, DB-facilitated protocol that could be adapted and shared for use by any clinical trial going forward.

项目摘要 这项研究（检测到AD或数字评估和技术，可实现AD的临床翻译） 目标是从根本上 无症状 改善对早期或早期的有意义认知功能的评估 阿尔茨海默氏病（AD）使用基于被动家庭的数字评估方法。 实现此目标，该方法将在使用A 当前，可共享的技术不可知论，基于家庭的评估平台，不断产生被动 和交互式传感器衍生的数字生物标志物（DB）和每天认知和功能的指标（数字 主动生活状态或拨号的指标）。该平台还允许远程捕获常规临床 评估。具有定义淀粉样蛋白状态的参与者（基于相对淀粉样蛋白PET的Aβ-HIGH与Aβ-LOW Burnens）将被注册。 Aβ高的参与者会像接受安慰剂一样发展。那些较低的人 Aβ伯良的进展将较小，模拟有效的治疗方法。会问参与者 将每日多种维生素作为研究“药物”以模仿试验条件。主要结果将是改变 来自四个关键领域的DB和复合拨号：移动速度（步态速度），认知（计算机使用）， 睡眠时间（睡眠时间），社交化（在家中时）。具体目的是：1）确定 DB（流动性，认知，睡眠和社交参与）单独，作为总指标（表盘） 在FDA阶段1-3 AD（Aβ-Highvs.Aβ-LOW）参与者中，通过建立早期基本率（前几个月 监测进展，然后是纵向变化； 2）建立这些DBS的实用性 试验中使用的常规措施（CDR-SOB，ADCS-PACC）； 3）调查探索目的 检查这些DBS在试验和相关研究中应用的几个高价值特征，包括：3.1） 将DBS和DIAL与常规成像和炎症的血液生物标志物相关联， 神经变性，血管风险或受伤以及营养健康； 3.2）确定随时间的变化 嵌入的“认知时钟”（是时候完成定期每周在线报告查询和每月认知的时间 测试）; 3.3）随着时间的流逝，建立不良事件的波动（情绪；疾病；疼痛；医生，医院就诊； 受伤;通过每周远程评估进行非研究用药更改）； 3.4）评估研究伙伴的 DBS相对于AD（流动性，睡眠，社交参与）的人而变化。 学习 那 成功完成 将提供经过基础验证的数据库和拨号数据，以改善治疗响应读数灵敏度； 提高AD临床试验能力和容量。目的不仅是验证单个应用程序或设备， 但是，要推进生态有效的多域评估以及整个试验 - 环境的特定于 DB实现的方案可以通过任何临床试验进行调整和共享。